Interspecies Variability in Biodistribution and PET Imaging Performance of [ 18 F]Di-PyL: A Dimeric, PSMA-Targeted PET Agent for Prostate Cancer

作者：Yimin Chen, Xiaojun Zhang, Xinlin Wang, Yachao Liu, Jinming Zhang, Mengchao Cui · 发表于：Journal of Nuclear Medicine · 年份：2025 · DOI：10.2967/jnumed.125.270069 · 被引用次数：6 · 研究领域：Cell Image Analysis Techniques、Evolution and Genetic Dynamics

Prostate cancer (PCa) is a leading cause of cancer deaths, making effective early detection, precise staging, and monitoring of biochemical recurrence crucial. Next-generation prostate-specific membrane antigen (PSMA) PET tracers could detect small or early metastatic lesion, especially in patients with low prostate-specific antigen. However, species differences in PSMA expression affect tracer biodistribution and imaging performance, highlighting the need for cross-species studies to optimize design and ensure clinical accuracy. Methods: We developed [ 18 F]Di-PyL, a dimeric, PSMA-targeted radiotracer based on the structure of [ 18 F]DCFPyL, and systematically evaluated the biodistribution of [ 18 F]Di-PyL in mice, pigs, dogs, and cynomolgus monkeys before conducting a preliminary imaging study in humans. The aim of these comparative analyses was to provide critical insights into the interspecies biodistribution and imaging performance of this dimeric agent, while highlighting its potential to improve the detection of PCa, particularly in patients with low prostate-specific antigen levels and biochemical recurrence. Results: [ 18 F]Di-PyL showed a 23-fold higher PSMA-binding affinity than did [ 18 F]DCFPyL. In vitro assays showed increased cellular uptake of [ 18 F]Di-PyL in PSMA-positive cells. Biodistribution studies revealed significant interspecies differences, with the kidneys showing the highest uptake across all species. Distinct uptake patterns were observed in t...